反应详情

温度

100 °C

To the DME solution of 3-methyl-2-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)benzofuran (2.3 mL, 0.58 mmol, 2 eq.) from the previous step were added 4-[4-(6-amino-5-bromopyridin-3-yl)-pyrazol-1-yl]piperidine-1-carboxylic acid tert-butyl ester (BB3) (120 mg, 0.29 mmol, 1 eq.), potassium carbonate (120 mg, 0.87 mmol, 3 eq.), water (0.5 mL), and 1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium DCM (10 mg, 0.01 mmol, 0.05 eq.). The mixture was evacuated and filled with nitrogen (3×) and heated in a microwave reactor to 100° C. for 30 min. The crude was passed through Thiol-SPE to remove Pd. The clear solution was purified with the MDPS. 1H NMR (400 MHz, CD3OD): δ=1.48 (s, 9H), 1.96 (dq, J=4.3, 12.3 Hz, 2H), 2.09 (br. s., 2H), 2.35 (s, 3H), 2.96 (br. s., 2H), 4.21 (br. s., 2H), 4.33-4.43 (m, 1H), 7.29 (dt, J=0.8, 7.4 Hz, 1H), 7.34 (dt, J=1.4, 7.2 Hz, 1H), 7.51 (d, J=7.8 Hz, 1H), 7.59-7.65 (m, 1H), 7.82 (s, 1H), 7.85 (d, J=2.3 Hz, 1H), 8.07 (s, 1H), 8.26 (d, J=2.3 Hz, 1H). MS (ES+): m/z=474.38 (100) [MH+]. HPLC: tR=0.94 min (UPLC-ACQUITY, Analytical).

1. customThe mixture was evacuated
2. additionfilled with nitrogen (3×)
3. customto remove Pd
4. customThe clear solution was purified with the MDPS